Levoketoconazole for treatment of congenital adrenal hyperplasia and primary aldosteronism
Disclosed are methods for treating congenital adrenal hyperplasia or primary aldosteronism in a subject in need thereof, comprising administering a therapeutically effective amount of 2S,4R ketoconazole enantiomer substantially free of the 2R,4S ketoconazole enantiomer to the subject. Also disclosed are compositions comprising a therapeutically effective amount of 2S,4R ketoconazole enantiomer substantially free of the 2R,4S ketoconazole enantiomer for use in treating a disease or condition associated with congenital adrenal hyperplasia or primary aldosteronism.
1. A method for treating congenital adrenal hyperplasia in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of 2S,4R ketoconazole enantiomer, wherein the ketoconazole content of the therapeutically effective amount comprises less than 20% 2R,4S enantiomer and more than 80% 2S,4R enantiomer, and wherein 11-deoxycortisol (11-DOC) secretion is not substantially increased after administration of the 2S, 4R ketoconazole enantiomer.
2. The method of claim 1 , wherein the congenital adrenal hyperplasia is due to 11-hydroxylase deficiency.
3. The method of claim 2 , wherein the congenital adrenal hyperplasia is of the classic form.
4. The method of claim 1 , wherein the therapeutically effective amount of the 2S,4R ketoconazole enantiomer is from about 50 mg to about 600 mg.
5. The method of claim 1 , wherein the therapeutically effective amount of the 2S,4R ketoconazole enantiomer is co-administered with one or more other active compounds selected from the group consisting of biguanides, sulfonylureas, HMG-COA reductase inhibitors, PPAR agonists, PTP-1B inhibitors, DPP-IV inhibitors, and anti-obesity compounds.
6. A composition for use in the method of claim 1 , the composition comprising a therapeutically effective amount of the 2S,4R ketoconazole enantiomer, wherein the ketoconazole content of the therapeutically effective amount comprises less than 20% 2R,4S enantiomer and more than 80% 2S,4R enantiomer.
7. The composition of claim 6 , wherein the therapeutically effective amount of the 2S,4R ketoconazole enantiomer is from about 50 mg to about 600 mg.
8. The composition of claim 6 , wherein the congenital adrenal hyperplasia is due to 11-hydroxylase deficiency.
9. The composition of claim 8 , wherein the congenital adrenal hyperplasia is of the classic form.
10. The composition of claim 6 , further comprising one or more active compounds other than the therapeutically effective amount of 2S,4R ketoconazole enantiomer, selected from the group consisting of biguanides, sulfonylureas, HMG-COA reductase inhibitors, PPAR agonists, PTP-1B inhibitors, DPP-IV inhibitors, and anti-obesity compounds.
11. A method for treating primary aldosteronism in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of 2S,4R ketoconazole enantiomer, wherein the ketoconazole content of the therapeutically effective amount comprises less than 20% of 2R,4S enantiomer and more than 80% of 2S,4R enantiomer, and wherein 11-DOC secretion is not substantially increased after administration of the 2S, 4R ketoconazole enantiomer.
12. The method of claim 11 , wherein the therapeutically effective amount of the 2S,4R ketoconazole enantiomer is from about 50 mg to about 600 mg.
13. The method of claim 11 , wherein the therapeutically effective amount of the 2S,4R ketoconazole enantiomer is co-administered with one or more other active compounds selected from the group consisting of biguanides, sulfonylureas, HMG-COA reductase inhibitors, PPAR agonists, PTP-1B inhibitors, DPP-IV inhibitors, and anti-obesity compounds.
14. A composition for use in the method of claim 11 , the composition comprising a therapeutically effective amount of the 2S,4R ketoconazole enantiomer, wherein the ketoconazole content of the therapeutically effective amount comprises less than 20% 2R,4S enantiomer and more than 80% 2S,4R enantiomer.
15. The composition of claim 14 , wherein the therapeutically effective amount of the 2S,4R ketoconazole enantiomer is from about 50 mg to about 600 mg.
16. The composition of claim 14 , further comprising one or more active compounds other than the therapeutically effective amount of 2S,4R ketoconazole enantiomer, selected from the group consisting of biguanides, sulfonylureas, HMG-COA reductase inhibitors, PPAR agonists, PTP-1B inhibitors, DPP-IV inhibitors, and anti-obesity compounds.